Planta Med 2013; 79 - PC10
DOI: 10.1055/s-0033-1348566

The Sesquiterpene Lactone Dehydroleucodine Shows Potent Anti-Leukemic Activity

PE Ordóñez 1, 3, 6, K Sharma 2, AB Martin 2, WF Reynolds 4, R Enriquez 5, O Malagón 3, DE Jones 6, ML Guzmán 2, CM Compadre 1
  • 1Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR
  • 2Weill Medical College, Cornell University, New York, NY
  • 3Universidad Técnica Particular de Loja, Ecuador
  • 4University of Toronto, Canada
  • 5Universidad Nacional Autónoma de México, Mexico
  • 6University of Arkansas at Little Rock, AR

Two known sesquiterpene lactones dehydroleucodine (1) and leucodine (2) were isolated from Gynoxys verrucosa, an herb used in traditional medicine in Southern Ecuador. Their anti-leukemic activity was determined against nine cell lines. Compound 1 showed LD50s between 0.11 and 3.99µM while compound 2 showed no activity, suggesting that the exocyclic conjugated methylene is required for the activity. In an effort to develop more water-soluble analogues of dehydroleucodine, adducts 3-6 were synthesized by a stereoselective conjugate addition of amines to the α-methylene-(γ-lactone moiety. The derivatives showed very low anti-leukemic activity. The structure of all compounds was established by spectroscopic methods and single-crystal X-ray crystallography.